前期研究表明osteopontin（OPN）是血管再狭窄的重要影响因子，激活NOD1/2/NF-кB介导的炎症反应也是血管再狭窄的重要始动因素，然而OPN在此病理过程中的分子机制尚不清楚。本课题利用大鼠移植静脉再狭窄模型和原代培养的大鼠血管平滑肌细胞、成纤维细胞、巨噬细胞为研究对象，采取慢病毒介导的OPN和其特异性siRNA转染的手段，并在干预免疫相关分子NOD1/2后，确证OPN在血管表型转化中生物学功能。分子机制上，从激活天然免疫应答介导的炎症反应的角度阐明激活NOD1/2/NF-кB/STAT3信号通路是调控血管再狭窄的重要分子机制，特别是阐明以NF-κB为调控中心的炎症反应是促进血管再狭窄的重要机制，进一步总结出OPN对该通路的调控作用。同时结合临床患者标本分析NOD1/2/NF-кB/STAT3通路中相关分子与移植静脉再狭窄的相关性，为下一步干预此通路防治血管再狭窄奠定理论基础。

Previous studies have shown that osteopontin (OPN) is an important molecular in promoting vascular restenosis, and activation of NOD1/2/NF-кB mediated inflammatory response is also an important initiating factor of vascular restenosis. However, the functional molecular mechanisms of OPN in this pathological process of vascular restenosis are not clear. This proposal is focused on studying the biological function of OPN in vascular phenotypic change. So the rat vein graft restenosis model and primary cultures of rat vascular smooth muscle cells, fibroblasts, macrophages are as the research objects, we then take the means of lentivirus-mediated OPN and its specific siRNA transfections, after the interference of immune moleculars NOD1, NOD2, confirmed that the biology function of OPN in the vascular restenosis. On the molecular mechanisms, from the perspective of activation of the innate immune response mediated inflammatory reaction to clarify activating NOD1/2/NF-кB/STAT3 signaling pathway is an important molecular mechanism of regulation of vascular restenosis, in particular, to clarify the control center of NF-κB mediated inflammatory response is the most important molecular mechanism of vascular restenosis, and further summed up the regulatory role of OPN in this pathway. Simultaneously, combined with clinical patient specimens analysis, the correlation of NOD1/2/NF-кB/STAT3 pathway related molecules and vein graft restenosis will be further analyzed, and these studies lay the theoretical foundation for the next step to intervene this signaling pathway to control vascular restenosis.